Statistical Models of Reconstructed Phase Spaces for Signal Classification

This paper introduces a novel approach to the analysis and classification of time series signals using statistical models of reconstructed phase spaces. With sufficient dimension, such reconstructed phase spaces are, with probability one, guaranteed to be topologically equivalent to the state dynamics of the generating system, and, therefore, may contain information that is absent in analysis and classification methods rooted in linear assumptions. Parametric and nonparametric distributions are introduced as statistical representations over the multidimensional reconstructed phase space, with classification accomplished through methods such as Bayes maximum likelihood and artificial neural networks (ANNs). The technique is demonstrated on heart arrhythmia classification and speech recognition. This new approach is shown to be a viable and effective alternative to traditional signal classification approaches, particularly for signals with strong nonlinear characteristics

Time-Domain Isolated Phoneme Classification Using Reconstructed Phase Spaces

This paper introduces a novel time-domain approach to modeling and classifying speech phoneme waveforms. The approach is based on statistical models of reconstructed phase spaces, which offer significant theoretical benefits as representations that are known to be topologically equivalent to the state dynamics of the underlying production system. The lag and dimension parameters of the reconstruction process for speech are examined in detail, comparing common estimation heuristics for these parameters with corresponding maximum likelihood recognition accuracy over the TIMIT data set. Overall accuracies are compared with a Mel-frequency cepstral baseline system across five different phonetic classes within TIMIT, and a composite classifier using both cepstral and phase space features is developed. Results indicate that although the accuracy of the phase space approach by itself is still currently below that of baseline cepstral methods, a combined approach is capable of increasing speaker independent phoneme accuracy

The synthesis and preliminary pharmacological screening of some benzoyl diamides of ethylenediamine and piperazine

Twelve N, N'-bis(hydroxy- and methoxybenzoyl)ethylenedi-amines and piperazines have been prepared, tested for antifungal activity, and screened for gross pharmacological activity in mice. All twelve compounds showed some activity against Candida albicans, Trichophyton mentagrophytes and Microsporum gypseum but in every case the activity was less than that of salicylanilide used as a control. In the test on mice N, N'-bis(4-hydroxybenzoyl)ethylenedaimine and N, N'-bis(3-methoxybenzoyl)piperazine showed activity (stimulation) after oral administration

Multiple congenital ocular anomalies in Icelandic horses

<p>Abstract</p> <p>Background</p> <p>Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color (<it>PMEL17</it>, exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another horse breed, the Icelandic horse, which is historically quite divergent from Rocky Mountain horses.</p> <p>Results</p> <p>We examined 24 Icelandic horses and established that the MCOA syndrome is present in this breed. Four of these horses were categorised as having the MCOA-phenotype and were genotyped as being homozygous for the <it>PMEL17 </it>mutation. The most common clinical signs included megaloglobus, iris stromal hypoplasia, abnormal pectinate ligaments, iridociliary cysts occasionally extending into the peripheral retina and cataracts. The cysts and pectinate ligament abnormalities were observed in the temporal quadrant of the eyes. Fourteen horses were heterozygous for the <it>PMEL17 </it>mutation and were characterized as having the Cyst-phenotype with cysts and occasionally curvilinear streaks in the peripheral retina. Three additional horses were genotyped as <it>PMEL17 </it>heterozygotes, but in these horses we were unable to detect cysts or other forms of anomalies.</p> <p>One eye of a severely vision-impaired 18 month-old stallion, homozygous for the <it>PMEL17 </it>mutation was examined by light microscopy. Redundant duplication of non-pigmented ciliary body epithelium, sometimes forming cysts bulging into the posterior chamber and localized areas of atrophy in the peripheral retina were seen.</p> <p>Conclusions</p> <p>The MCOA syndrome is segregating with the <it>PMEL17 </it>mutation in the Icelandic Horse population. This needs to be taken into consideration in breeding decisions and highlights the fact that MCOA syndrome is present in a breed that are more ancient and not closely related to the Rocky Mountain Horse breed.</p

The spatial effect of protein deuteration on nitroxide spin-label relaxation:implications for EPR distance measurement

This work was supported by a Wellcome Trust Senior Fellowship (095062) to T.O.-H. The Authors would also like to acknowledge funding from The MRC – United Kingdom, Grant G1100021.Pulsed electron-electron double resonance (PELDOR) coupled with site-directed spin labeling is a powerful technique for the elucidation of protein or nucleic acid, macromolecular structure and interactions. The intrinsic high sensitivity of electron paramagnetic resonance enables measurement on small quantities of bio-macromolecules, however short relaxation times impose a limit on the sensitivity and size of distances that can be measured using this technique. The persistence of the electron spin-echo, in the PELDOR experiment, is one of the most crucial limitations to distance measurement. At a temperature of around 50 K one of the predominant factors affecting persistence of an echo, and as such, the sensitivity and measurable distance between spin labels, is the electron spin echo dephasing time (Tm). It has become normal practice to use deuterated solvents to extend Tm and recently it has been demonstrated that deuteration of the underlying protein significantly extends Tm. Here we examine the spatial effect of segmental deuteration of the underlying protein, and also explore the concentration and temperature dependence of highly deuterated systems.Publisher PDFPeer reviewe

Normalization of Illumina Infinium whole-genome SNP data improves copy number estimates and allelic intensity ratios

<p>Abstract</p> <p>Background</p> <p>Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples.</p> <p>Results</p> <p>We demonstrate an asymmetry in the detection of the two alleles for each SNP, which deleteriously influences both allelic proportions and copy number estimates. The asymmetry is caused by a remaining bias between the two dyes used in the Infinium II assay after using the normalization method in Illumina's proprietary software (BeadStudio). We propose a quantile normalization strategy for correction of this dye bias. We tested the normalization strategy using 535 individual hybridizations from 10 data sets from the analysis of cancer genomes and normal blood samples generated on Illumina Infinium II 300 k version 1 and 2, 370 k and 550 k BeadChips. We show that the proposed normalization strategy successfully removes asymmetry in estimates of both allelic proportions and copy numbers. Additionally, the normalization strategy reduces the technical variation for copy number estimates while retaining the response to copy number alterations.</p> <p>Conclusion</p> <p>The proposed normalization strategy represents a valuable tool that improves the quality of data obtained from Illumina Infinium arrays, in particular when used for LOH and copy number variation studies.</p

Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays

A strategy is presented for detection of loss-of-heterozygosity and allelic imbalance in cancer cells from whole genome SNP genotyping data

The Constitutional Politics Heller Launched

Antibiotic resistance in bacteria causing disease is an ever growing threat to the world. Recently, environmental bacteria have become established as important both as sources of antibiotic resistance genes and in disseminating resistance genes. Low levels of antibiotics and other pharmaceuticals are regularly released into water environments via wastewater, and the concern is that such environmental contamination may serve to create hotspots for antibiotic resistance gene selection and dissemination. In this study, microcosms were created from water and sediments gathered from a lake in Sweden only lightly affected by human activities. The microcosms were exposed to a mixture of antibiotics of varying environmentally relevant concentrations (i.e., concentrations commonly encountered in wastewaters) in order to investigate the effect of low levels of antibiotics on antibiotic resistance gene abundances and dynamics in a previously uncontaminated environment. Antibiotic concentrations were measured using liquid chromatography-tandem mass spectrometry. Abundances of seven antibiotic resistance genes and the class 1 integron integrase gene, intL1, were quantified using real-time PCR. Resistance genes sulI and ermB were quantified in the microcosm sediments with mean abundances 5 and 15 gene copies/10(6) 16S rRNA gene copies, respectively. Class 1 integrons were determined in the sediments with a mean concentration of 3.86x10(4) copies/10(6) 16S rRNA gene copies. The antibiotic treatment had no observable effect on antibiotic resistance gene or integron abundances

Methyl sulfonamide substituents improve the pharmacokinetic properties of bicyclic 2-pyridone based:Chlamydia trachomatis inhibitors

Chlamydia trachomatis infections are a global health problem and new approaches to treat C. trachomatis with drugs of high specificity would be valuable. A library of substituted ring fused 2-pyridones has been synthesized and evaluated for their ability to attenuate C. trachomatis infectivity. In vivo pharmacokinetic studies were performed, with the best candidates demonstrating that a C8-methylsulfonamide substituent improved pharmacokinetic properties important for oral administration. C8-Methyl sulfonamide analogue 30 inhibited C. trachomatis infectivity in low micromolar concentrations. Further pharmacokinetic evaluation at an oral dose of 10 mg kg(-1) showed an apparent bioavailability of 41%, compared to C8-cyclopropyl and -methoxy analogues which had negligible oral uptake. In vitro ADME (absorption, distribution, metabolism and excretion) testing of solubility and Caco-2 cell permeability revealed that both solubility and permeability is greatly improved with the C8-methyl sulfonamide 30, effectively moving it from BCS (Biopharmaceutical Classification System) class IV to II

Recommendations for Medical Management of Adult Lead Exposure

Research conducted in recent years has increased public health concern about the toxicity of lead at low dose and has supported a reappraisal of the levels of lead exposure that may be safely tolerated in the workplace. In this article, which appears as part of a mini-monograph on adult lead exposure, we summarize a body of published literature that establishes the potential for hypertension, effects on renal function, cognitive dysfunction, and adverse female reproductive outcome in adults with whole-blood lead concentrations < 40 μg/dL. Based on this literature, and our collective experience in evaluating lead-exposed adults, we recommend that individuals be removed from occupational lead exposure if a single blood lead concentration exceeds 30 μg/dL or if two successive blood lead concentrations measured over a 4-week interval are ≥ 20 μg/dL. Removal of individuals from lead exposure should be considered to avoid long-term risk to health if exposure control measures over an extended period do not decrease blood lead concentrations to < 10 μg/dL or if selected medical conditions exist that would increase the risk of continued exposure. Recommended medical surveillance for all lead-exposed workers should include quarterly blood lead measurements for individuals with blood lead concentrations between 10 and 19 μg/dL, and semiannual blood lead measurements when sustained blood lead concentrations are < 10 μg/dL. It is advisable for pregnant women to avoid occupational or avocational lead exposure that would result in blood lead concentrations > 5 μg/dL. Chelation may have an adjunctive role in the medical management of highly exposed adults with symptomatic lead intoxication but is not recommended for asymptomatic individuals with low blood lead concentrations